Semaphorins and their receptors in stem and cancer cells.

There is a growing body of evidence that links cancer with genes and pathways that are required for normal embryonic development, increasing the possibility that cancer cells with stem cell properties, particularly self-renewal and multipotentiality, are primarily involved in tumor formation and progression. One novel pathway that is important in regulating the morphogenesis, proliferation, survival and growth in a variety of adult and embryonic tissues is the semaphoring signaling pathway. Semaphorins are a large family of secreted, transmembrane and GPI-linked proteins with a broad spectrum of functions. Semaphorin signaling is transduced by plexins which, in the case of most class 3 semaphorins, require high affinity neuropilin receptors. The neuropilins also function as receptors for VEGF and other growth factors, and their expression is abnormal in tumors. Various semaphorins can either promote or inhibit tumor progression through the promotion or inhibition of processes such as tumor angiogenesis, metastasis and tumor cell survival. In normal tissues, semaphoring signaling is mainly active in precursor cells. This increases the possibility of tumors being derived from such cells, possibly even stem cells, which are unable to differentiate and/or to stop proliferating. In this review, we summarize the molecular mechanisms of semaphorin signal transduction involved in the stem cell compartment, and describe the evidence that links semaphorins to the control of tumor progression.

The effects of insulin and insulin-like growth factors on tumor vascularization: new insights of insulin-like growth factor family in cancer.

It is currently believed that the development of a clinically relevant tumor needs new vessel formation provided by both angiogenesis (primary involving endothelial cells) and postnatal vasculogenesis (primary involving bone marrow-derived cells). Clearly, it is important to identify factors that help to enhance the growth and "health" of tumors, as well as their further vascularization. The Insulin and Insulin-like Growth Factors (IGFs) systems play a key role in cellular metabolism, differentiation, proliferation, transformation and apoptosis, during normal and malignant growth. Moreover, these molecules seem essential in promoting tumor vascularization. Due to the complexity of these systems, the review has been focused on the role of insulin and IGFs signaling in the regulation of tumor angiogenesis and postnatal vasculogenesis. Since targeting on IGF for cancer therapy is rapidly becoming a clinical reality, a better understanding of IGFs-mediated pathways has a relevant impact, providing new insights to help the design of newly developed drugs.